PaXoret-1-Co 1k ZU 11 aod LU) Prevencion primaria de muerte subita cardiaca en pacientes con miocardiopatia e insuficiencia cardiaca con FEVI reducida Autores: Joseph E Marine, MD, FAC, FHRS, Andrea M Russo, MD, FACC, FHRS Editores de seccién: Samuel Lévy, MD, Bradley P Knight, MD, FACC Editor adjunto: Susan 8 Yeon, MD, JD, FACC Todos los temas se actualizan a medida que se dispone de nueva evidencia y se completa nuestro proceso de revisién por pares Revisién de la literatura vigente hasta: diciembre de 2020, | Este tema se actualizé por ditima vez: 10 de julio de 2020, INTRODUCCION Las arritmias ventriculares potencialmente mortales, incluidas la taquicardia ventricular sostenida (TV) y la fibrilacién ventricular (FV), son frecuentes en pacientes con insuficiencia cardiaca sistélica (IC) y miocardiopatia dilatada y pueden provocar muerte cardiaca subita (MSC). La prevencién primaria de la ECF se refiere ala terapia médica o intervencionista realizada para prevenir la ECF en pacientes que no han experimentado una TV / FV sostenida sintomatica y potencialmente mortal o un paro cardiaco repentino (PCS), pero que se considera que tienen un mayor riesgo de tal evento. La prevencién primaria de la MSC en pacientes con IC y miocardiopatia con fraccién de eyeccién reducida, ya sea por enfermedad coronaria o por una etiologia no isquémica dilatada, se revisard aqui con énfasis en el papel de los desfibriladores automiticos implantables (DAI). Los diferentes tipos de arritmias ventriculares, los efectos del tratamiento de la insuficiencia cardiaca en las arritmias ventriculares, la funcién de las pruebas electrofisiolégicas y la prevencién secundaria de la ECF se analizan por separado. (Ve ventriculares: Resumen en pacientes con insuficiencia cardiaca y miocardiopatia"y “Prevencién dari a ici fi jopatia" .) Los enfoques para el tratamiento de las arritmias ventriculares relacionadas con enfermedades especificas del mtisculo cardiaco o enfermedades primarias del sistema eléctrico, como la miocardiopatia hipertréfica, la miocardiopatia arritmogénica del ventriculo derecho, la no compactacién aislada del ventriculo izquierdo, la enfermedad de Chagas, el sindrome de Brugada, el sindrome de QT largo y otras canalopatias, se describen en otro lugar. .PaXoret-1-Co 1k ZU 11 aod LU) diagnéstico” ), * (Ver “Miocardiopatia Chagas crénica: manejo y prondstico" ), * (Ver "Sindrome de Brugada: pronéstico, manejo y enfoque del cribado" ). * (Consulte "Sindrome de QT largo congénito: tratamiento" ). CAUSAS DE MUERTE POR INSUFICIENCIA CARDIACA Las causas de muerte en pacientes con insuficiencia cardiaca incluyen: * Fallo progresivo de la bornba + MSC inesperada (generalmente por una taquiarritmia ventricular, pero la asistolia y la actividad eléctrica sin pulso [PEA] también se observan con menos frecuencia) + SCD en el contexto de empeoramiento de la insuficiencia cardiaca Es mas probable que el modo de muerte en pacientes con IC sea "repentino" en pacientes con IC de clase II 0 Ill, mientras que el modo de muerte es mas probable que esté relacionado con la falla de la "bomba' en pacientes con IC de clase IV (Ad Figura 1) [ 1]. Por tanto, los ensayos de prevencién primaria con desfibrilador automatico implantable (DAN) (en ausencia de terapia de resincronizacién cardiaca [TRC)) han excluido a los pacientes con IC de clase IV de la NYHA. De hecho, las directrices de la American Heart Association / American College of Cardiology / Heart Rhythm Society (AHA / ACC / HRS) de 2017 establecen que "la terapia con DAI no esta indicada para pacientes de clase IV de la NYHA con IC refractaria a los medicamentos que no son candidatos a trasplante, un DAVI (dispositivo de asistencia ventricular izquierda) 0 TRC-D", que lo enumera como una indicacién de clase Il [2 ]. (Consulte ‘Insuficiencia cardiaca de clase IV'a continuacién y “Trasplante de corazén en adultos: indicaciones y contraindicaciones" y"Terapia de resincronizacién cardiaca en insuficiencia cardiaca: indicaciones" .) ESTRATEGIAS DE ESTRATIFICACION DE RIESGOS Si bien los desfibriladores automaticos implantables (DAI) son muy eficaces en el tratamiento de las taquiarritmias ventriculares y la prevencién de la ECF, son costosos, requieren un seguimiento continuo y presentan numerosos riesgos en el momento de la implantacién (p. Ej., Hemorragia, neumotérax, perforacién, etc.) asi como durante la vida Util del dispositivo (por ejemplo, infeccién, mal funcionamiento del dispositive y del cable, etc.). Ademés, solo un subconjunto de pacientes con miocardiopatia desarrolla taquiarritmias ventriculares sostenidas © SCD. Como tal, la estratificacién del riesgo de los pacientes antes de la terapia con DAL esPaNoret-1-1o ka ZU 181 aod LU) intentos para desarrollar un esquema de estratificacién del riesgo para identificar mas especificamente el riesgo de SCD de un paciente individual. Sin embargo, hasta la fecha, el enfoque éptimo para la estratificacién del riesgo de ECF para la colocacién de un DAI de prevencién primaria continua basandose principalmente en lo siguiente: + Etiologia de la disfuncién ventricular izquierda + Fraccién de eyeccién del ventriculo izquierdo Clasificacién de los sintomas de insuficiencia cardiaca Esperanza de vida superior a un ao * Taquicardia ventricular sostenida inducible Taquicardia ventricular no sostenida en la monitorizaci6n del electrocardiograma (ECG) FEVIy riesgo : los pacientes con reducciones significativas de la fraccién de eyeccién del ventriculo izquierdo (FEVI) parecen estar en mayor riesgo y obtienen el mayor beneficio del implante de DAT en prevencién primaria. (Consulte ‘Ensayos de ICD de prevencién primaria en miocardiopatia isquémica' a continuacién y ‘Ensayos de ICD de prevencién primaria en miocardiopatia dilatada no isquémica' a continuacién). Aunque la mayoria de los estudios de implantacién profilactica de DAI han incluido pacientes con una FEVI <35 por ciento, la gran mayoria de los pacientes incluidos en la mayoria de los ensayos han tenido fracciones de eyeccién por debajo del 30 por ciento, lo que genera cierta incertidumbre sobre el beneficio potencial de la insercién profilactica de DAI para pacientes con FEVI entre 30 y 35 por ciento. Este problema se abordé en un estudio de cohorte retrospective utilizando datos de registro del registro NCDR ICD de pacientes que se sometieron a la implantacién de un ICD en 2006 0 2007 (seguimiento medio de 4,4 afios) y de pacientes con insuficiencia cardiaca (GWTG-HF) sin un DAI (inscrito entre 2005 y 2009 con una mediana de seguimiento de 2,9 afios), en el que los beneficios de la implantacién de un DAI se evaluaron por separado entre los pacientes con FEVI <30 por ciento y aquellos con FEVI del 30 al 35 por ciento [3]. La mortalidad por todas las causas fue significativamente menor en pacientes con un DAL cualquier nivel de FEVI, en comparacién con aquellos sin DAI: * FEVI 30 a 35 por ciento - HR 0,83, IC del 95% 0,69-0,99 * FEVI <30 por ciento - HR 0,72, IC 95% 0,65-0,81 Si bien este estudio no es aleatorio, los datos sugieren que los pacientes con FEVI entre el 30y el 35 por ciento parecen beneficiarse de la insercién profildctica de un DAI. SCD pre como un medio para la identificacién de los pacientes en el mayor riesgo de SCD después de un n de riesgo post-MI - Un ntimero de caracteristicas clinicas se han evaluadoPaXoret-1-Co 1k ZU 11 aod LU) * Ondas Q en el ECG de superficie * Retraso de la conduccién intraventricular * Latidos ventriculares prematuros esponténeos (VPB) y taquicardia ventricular no sostenida (NSVT) Potenciales tardios en un ECG de sefial promediada (SAECG) TV inducida por estudio electrofisiolégico (EPS) Variabilidad reducida de la frecuencia cardiaca (VFC) Alternancia de onda T de microvoltios (repolarizacian) (TWA) Una discusién detallada de la utilidad de estos predictores clinicos se presenta por separado. (Consulte "Incidencia y estratificacién del riesgo de muerte subita cardiaca después de un infarto de miocardio" ). Marcadores de riesgo clinico : una variedad de nuevos esquemas de estratificacién del riesgo derivados de estudios retrospectivos han demostrado la capacidad de predecir el riesgo de MSC, pero ninguno ha sido validado prospectivamente en poblaciones independientes o se ha convertido en parte de la practica habitual para la colocacién de DAl en prevencién primaria [ 4-13]. Por tanto, la estratificacién del riesgo tradicional basada en la etiologia de la miocardiopatia, la FEVI, la clase de IC y otros marcadores de riesgo seleccionados (p. ., Arritmias ventriculares sostenidas inducibles) sigue constituyendo la base de las. recomendaciones sobre el uso de DAI. Los estudios iniciales que evaluaron el papel de la terapia con DAl en la reduccién de la mortalidad se centraron en pacientes con funcién sistélica del VI reducida e insuficiencia cardiaca de clase II-II]. Dado que el modo de muerte en pacientes con insuficiencia cardiaca de clase II-III fue mas probable de forma repentina (entre el 59 y el 64 por ciento de los casos [ 1]), los criterios de inscripcién para los ensayos de ICD incluian a menudo a pacientes con sintomas de IC de clase II-III. En contraste, los pacientes con insuficiencia cardiaca de clase IV tenian mas probabilidades de morir por insuficiencia cardiaca (56 por ciento) que por muerte suibita (33 por ciento). Los estudios que examinaron la relacién entre la mortalidad a un afio y la funcién del VI después de un infarto de miocardio en la era pre y postrombolitica demostraron una tasa de mortalidad cardiaca mucho més alta en pacientes con FEVI <40% [ 14,15]. La presencia de NSVT © ectopia ventricular frecuente también se asocié con un aumento de la mortalidad después del IM, por lo que la NSVT también se utiliz6 como factor de riesgo para su inclusion en algunos de los ensayos aleatorizados de DAI. Estudios anteriores también demostraron que la TV monomérfica sostenida inducible se asociaba con un mayor riesgo de muerte stbita o arritmias ventriculares sostenidas [ 16 }PaXoret-1-Co 1k ZU 11 aod LU) ciento. + Una revisién sistematica y un metandlisis de 2017, que incluyé 2948 pacientes de 29 estudios observacionales, evalué la relacién entre el RTG y las arritmias ventriculares en pacientes con miocardiopatia dilatada no isquémica [ 17 ]. Durante un seguimiento medio de tres afios, el criterio de valoracién principal (arritmia ventricular sostenida, intervencion adecuada del DAI 0 MSC) se presents en 350 pacientes, incluido el 21 por ciento de los pacientes con RTG (en comparacién con el 4,7 por ciento de los pacientes sin RTG; razén de posibilidades agrupada [OR] 4,3; IC del 95%: 3,3-5,8). LGE pudo estratificar el riesgo de los pacientes en todos los niveles de FEVI (tanto por encima como por debajo del 35 por ciento) y fue mas poderoso entre los pacientes con DAI colocados previamente para prevencién primaria (OR 7,8; IC de! 95%: 1,7-35,8). * En un estudio australiano, no aleatorizado, prospectivo de 2019 de 452 pacientes con miocardiopatia no isquémica (FEVI < 35 por ciento) que se habian sometido a una RMC y que cumplian con los criterios de la ESC / AHA para la colocacién de un DAI de prevencién primaria, la mitad recibié un DAI de prevencién primaria de acuerdo con el juicio del médico tratante y practica local predominante [ 18 ]. Los pacientes con fibrosis miocardica (manifestada por LGE en la RMC) que recibieron un DAI tuvieron una mortalidad més baja que los que no recibieron un DAI (HR 0,45; IC del 95%: 0,26 a 0,77). Sin embargo, no hubo diferencia en la supervivencia con o sin un DAI para los 175 pacientes sin fibrosis miocérdica. El estudio MARVEN (factores de riesgo clinicos, electrocardiograficos y de resonancia magnética cardiaca asociados con taquiarritmias ventriculares en miocardiopatia no isquémica) es un estudio observacional prospectivo patrocinado por el NHLBI cuyo objetivo es desarrollar estrategias optimas de estratificacién del riesgo para predecir taquiarritmias ventriculares en pacientes con miocardiopatia CR no isquémica. -D implantacién para determinar si LGE-CMR mejorar aun mas la estratificacién del riesgo en pacientes con miocardiopatia no isquémica, FEVI < 35% y QRS > 120 milisegundos [ 19 }. Si bien no se utiliza actualmente en las pautas de estratificacién del riesgo de SCD, si estos datos se confirman en estudios prospectivos adicionales, entonces LGE en CMR puede convertirse en un criterio utilizado en futuros esquemas de estratificacién del riesgo. USO DE UN ICD Las arritmias ventriculares malignas que pueden conducir a MSC se observan con mas frecuencia en pacientes con ciertas miocardiopatias (en comparacién con la poblacién general),PaNoret-1-1o ka ZU 181 aod LU) betabloqueantes no parecen mejorar los resultados. (Ver "Prevencién secundaria de muerte cardiaca subita en insuficiencia cardiaca y cardiomiopatia" .) El papel de un DAI en la prevencién primaria de la ECF en pacientes con IC y miocardiopatia depende de varios factores: + La gravedad de la disfuncién sistélica del ventriculo izquierdo (VI) * La gravedad de la IC clinica (3 Tabla 2) * La etiologia de la disfuncién del VI (es decir, miocardiopatia isquémica o no isquémica) * Comorbilidades competitivas que afectan la longevidad y el riesgo de complicaciones del ICD (p. Ej., Enfermedad renal crénica, enfermedad pulmonar obstructiva crénica, etc.) El riesgo de MSC aumenta con la gravedad de la disfuncién sistdlica del VI y de la IC clinica [ 20 ]. Sin embargo, el riesgo de muerte por otras causas (p. Ej., Insuficiencia cardiaca progresiva) también aumenta con el empeoramiento de la insuficiencia cardiaca y la disfuncién sistélica del VI, lo que refuerza la importancia de una seleccién adecuada de los pacientes antes de la colocacién de un DAI en prevencién primaria. (Ver "Prevencién secundaria de muerte cardiaca sbita en insuficiencia cardiaca y cardiomiopatia'", seccién sobre ‘Epidemiologia' ). Cardiac resynchronization therapy (CRT) may be appropriate treatment for selected HF patients with ischemic or non-ischemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF) (<35 percent) with a wide QRS complex (especially if left bundle branch block QRS morphology), if left ventricular function does not improve with guideline-directed medical therapy. Ventricular dyssynchrony refers to the loss of coordinated contraction across the left ventricle. Dyssynchrony can further impair the pump function of a failing ventricle and exacerbate HF symptoms. CRT can improve pump performance, reverse the deleterious process of ventricular remodeling, and improve survival in appropriately selected patients. CRT can be achieved with a device designed for pacing only (CRT-P) or can be incorporated into a combination device with an ICD (CRT-D) (4 figure 2) [21]. (See "Cardiac resynchronization therapy in heart failure: Indications".) Ischemic cardiomyopathy Our approach for patients with ischemic cardiomyopathy — We recommend ICD therapy for primary prevention of SCD in the following groups of patients with ischemic cardiomyopathy: * For patients with cardiomyopathy due to ischemic heart disease, left ventricular ejection fraction (LVEF) $35 percent, and associated HF with New York Heart Association (NYHA) functional class II or III status [2]PaNoret-1-1o ka ZU 181 aod LU) medical therapy. These restrictions recognize that revascularization and medical therapy may result in significant improvement in LVEF and/or HF class. + For patients with nonsustained ventricular tachycardia (NSVT) associated with prior MI, LVEF <40 percent, and inducible sustained VT or ventricular fibrillation at electrophysiology study [2,22,23]. Patients should be past the acute phase of MI, on guideline-directed medical therapy, and have reasonable expectation for survival for at least one year. Patients who have had an MI resulting in reduced LVEF are at increased risk of SCD, most often due to a ventricular tachyarrhythmia. Prophylactic ICD implantation for the primary prevention of SCD reduces mortality in selected patients with ischemic cardiomyopathy. Coronary revascularization itself may also reduce the future risk of malignant arrhythmias and SCD, as. shown in the early versus late ICD implantation strategies and differing results in various randomized trials, The best approach to selecting patients with ischemic cardiomyopathy for ICD therapy for primary prevention has been explored in several major randomized trials, with the indications for ICD implantation derived largely from the inclusion criteria of these trials. One caveat, however, is that these trials took place prior to the contemporary guideline-based approaches to optimal medical therapy for patients with heart failure and cardiomyopathy. Trials of primary prevention ICDs in ischemic cardiomyopathy MADIT-I trial — The Multicenter Automatic Defibrillator Implantation Trial (MADIT, now called MADIT-1) was the first trial to demonstrate that the ICD has a role in primary prevention of SCD in certain high-risk, asymptomatic patients [22]. Patients had a prior MI with reduced LVEF (<35 percent), NSVT on ECG monitoring, and inducible sustained monomorphic VT during electrophysiology study (EPS) that was also inducible after administration of intravenous procainamide, Among 196 patients who were randomly assigned to pharmacologic therapy (including an antiarrhythmic drug at the discretion of the clinician, with amiodarone administered to most patients) or an ICD and followed for an average of 27 months, patients assigned to ICD therapy had significant reductions in overall mortality, cardiac mortality, and arrhythmic deaths compared with patients assigned to medical therapy (J figure 3). While the MADIT-I trial remains an important landmark study in the utilization of ICDs for primary prevention, it has largely been supplanted by subsequent studies with larger numbers of patients, better methodologies, and simpler risk stratification schemes for study entry. MUSTT trial — The Multicenter Unsustained Tachycardia Trial (MUSTT trial), which was not primarily designed as a randomized ICD clinical trial but rather to study the management of high-risk patients using the results of electrophysiology study (EPS), enrolled patients with prior MI, reduced LVEF (<40 percent), asymptomatic NSVT on ECG monitoring, inducible sustained VTPaXoret-1-Co 1k ZU 11 aod LU) least one antiarrhythmic agent was ineffective. After a median follow-up of 39 months, the five- year (25 versus 32 percent, relative risk [RR] 0.73, 95% CI 0.53-0.99) rates for the primary endpoint (arrhythmic death or resuscitated SCD) were significantly lower for EPS-guided therapy compared with standard medical therapy. The reduction in the primary endpoint in the EPS-guided group was largely attributable to ICD therapy; at five years, the primary endpoint occurred in 9 percent of those receiving an ICD, compared with 37 percent of those receiving an antiarrhythmic drug (RR 0.24, 95% CI 0.13-0.45) (4 figure 4). Whether inducible arrhythmia might be prognostically important in patients with an LVEF of 30 to 40 percent was addressed in another analysis from MUSTT [24]. The rate of arrhythmic death at five years was significantly increased for patients with inducible VT and LVEF between 30 and 40 percent, suggesting that for patients with LVEF 230 percent only, electrophysiology testing may have useful predictive value. CABG Patch trial — The Coronary Artery Bypass Graft (CABG) Patch trial evaluated the efficacy of an epicardial ICD implanted at the time of coronary artery bypass graft surgery among 900 patients with severe coronary artery disease (CAD), reduced LVEF <36 percent, abnormal signal averaged ECG, and no prior sustained VT or syncope [25]. Epicardial ICD systems were predominantly used, Compared with standard medical therapy over an average of 32 months, there was no significant difference in overall or cardiovascular mortality among patients with an ICD (HR 1.07 for overall mortality compared with standard medical therapy, 95% CI 0.81-1.42) (figure 5). This negative trial is a primary reason why current guidelines recommend against primary prevention ICD implantation for patients who have recently undergone coronary revascularization, as revascularization itself may reduce the future risk of malignant arrhythmias and SCD. MADT-II trial — The Multicenter Automatic Defibrillator Implantation Trial Il (MADIT-II) enrolled 1232 patients with a prior MI more than 30 days prior to enrollment (and more than three months if bypass surgery was performed) and reduced LVEF (<30 percent); NSVT and inducible VT during EPS were not required [26]. The study, which randomly assigned patients to a prophylactic ICD or conventional medical therapy, was stopped early due to benefit of ICD therapy after an average follow-up of 20 months. Patients in the ICD group had reduced all- cause mortality (14.2 versus 19.8 percent for conventional therapy, hazard ratio [HR] 0.65, 95% 1.0.51-0.93) (Mi figure 6). SCD-HeFT trial — The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which evaluated ICD and amiodarone therapies in patients with both ischemic (52 percent) or nonischemic (48 percent) cardiomyopathy, enrolled patients with NYHA class II or III heartPaolo 1-10 ok ZU 11 aod LU) * Congestive heart failure (CHF) present for at least three months prior to randomization and treated with ACE inhibitor and beta-blocker, if tolerated Among 2521 patients who were randomly assigned to ICD implantation, amiodarone, or placebo, and followed for a median of 46 months, total mortality at five years was significantly reduced with ICD therapy (29 versus 36 percent with placebo, HR 0.77, 95% CI 0.62-0.96). The benefit of an ICD was comparable among patients with either an ischemic or nonischemic cardiomyopathy. A long-term analysis of SCD-HeFT participants, published in July 2020, showed continued survival benefit in the ICD arm over placebo arm at a median follow-up of 11 years (HR: 0.87; 95% CI 0.76-0.98) [28]. Long-term benefit was most evident for patients with ischemic cardiomyopathy and those with NYHA functional class II symptoms at enrollment. These results suggest that an ICD is beneficial in patients with chronic HF and a diminished LVEF (535 percent), despite appropriate medical therapy for at least three months. In contrast, amiodarone provided no benefit over placebo. DINAMIT trial — The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT), which evaluated the role of prophylactic ICD implantation compared with standard medical therapy, enrolled 674 patients with MI in the preceding 6 to 40 days (mean of 18 days), reduced LVEF (<35 percent), and reduced heart rate variability or elevated resting heart rate (280 beats/minute) [29]. Patients with sustained VT >48 hours post-MI, NYHA class IV HF, or CABG or three-vessel percutaneous coronary intervention post-MI were excluded. After a mean follow- up of 30 months, there was no significant difference in annual all-cause mortality between the patients with and without an ICD (7.5 versus 6.9 percent annual mortality, HR 1.08, 95% CI 0.76- 1.55). This negative trial provides an important rationale for the current guideline recommendation that ICD implantation should be deferred until at least 40 days after an MI. IRIS trial — The Immediate Risk Stratification Improves Survival (IRIS) trial also evaluated the efficacy of ICD therapy versus standard therapy early post-MI and enrolled patients with an MI in the preceding 5 to 31 days and at least one of the following: reduced LVEF (<40 percent) with a resting heart rate 290 beats/minute or NSVT at a rate of 2150 beats/minute or both [30]. Among 898 randomized patients who were followed for an average of 37 months, there was no difference in all-cause mortality between patients randomly assigned to ICD therapy and those assigned to medical therapy (HR 1.04 for ICD therapy, 95% CI 0.81-1.35). Nonischemic dilated cardiomyopathy Our approach for patients with nonischemic dilated cardiomyopathy — We recommend ICD therapy for primary prevention of SCD in the following groups of patients with nonischemicPaNoret-1-1o ka ZU 181 aod LU) * For most patients with LVEF $35 percent, class III or IV HF, and a QRS duration 2120 milliseconds (especially if left bundle branch block [LBBB] QRS morphology), we recommend implantation of a combined CRT-D device (biventricular pacing combined with an ICD). + Additionally, many patients with specific non-ischemic cardiomyopathies (eg, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, cardiac amyloidosis, etc) may be candidates for primary prevention ICD based on disease-specific risk markers. The approaches to selection of appropriate patients in a variety of conditions are discussed in the individual UpToDate topics. Ventricular arrhythmias are common in patients with HF and a nonischemic cardiomyopathy. While some small early trials suggested no benefit of ICD therapy in patients with nonischemic cardiomyopathy, subsequent larger trials and a 2004 meta-analysis have demonstrated greater overall survival following prophylactic ICD implantation in selected patients. While ICDs effectively reduce mortality from SCD, the benefit on total mortality appears diminished in the setting of optimal guideline-directed medical therapy and CRT. (See "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy".) Trials of primary prevention ICDs in nonischemic dilated cardiomyopathy DEFINITE trial — The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial evaluated the efficacy of an ICD versus standard medical therapy, in 458 patients with nonischemic dilated cardiomyopathy, reduced LVEF (<35 percent), and premature ventricular beats or NSVT [31]. After mean follow-up of 29 months, there was a trend toward reduction in the primary endpoint of all-cause mortality in patients treated with an ICD (7.9 versus 14.1 percent with medical therapy alone, HR 0.65, 95% CI 0.40-1.06). Fewer sudden deaths occurred in the ICD arm, although the numbers were very small (3 deaths versus 14 deaths in the medical therapy arm, HR 0.20, 95% CI 0.06-0.71). The all-cause mortality rate in the "medical therapy only” arm of DEFINITE (14.1 percent at two years) was lower than had been anticipated when the study was designed, potentially contributing to the trial being underpowered for its primary endpoint. SCD-HeFT trial — The Sudden Cardiac Death in Heart Failure trial (SCD-HeFT), which evaluated ICD and amiodarone therapies in patients with both ischemic (52 percent) or nonischemic (48 percent) cardiomyopathy, identified a significant reduction in overall mortality with ICD therapy (29 versus 36 percent with placebo, HR 0.77, 95% CI 0.62-0.96) [27]. ThePaNoret-1-1o ka ZU 181 aod LU) of a combined CRT-D device (biventricular pacing combined with an ICD) [32.33]. The benefit appears to be greatest in patients with a left bundle branch block and QRS duration 2150 milliseconds [34-36]. Patients with right bundle branch block and a QRS duration <150 ms are much less likely to benefit from CRT. The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial evaluated optimal medical therapy versus CRT with or without an ICD among 682 patients with nonischemic dilated cardiomyopathy, reduced LVEF (<35 percent), and NYHA class III or IV HF symptoms requiring hospitalization within the prior year [33]. After median follow-up of 16 months, there was a significant reduction in the incidence of the combined endpoint of all- cause mortality and all-cause hospitalization in the two arms receiving CRT compared with the medical therapy only arm (56 versus 68 percent). The CRT-D arm, but not the CRT-P arm, experienced a significant improvement in the secondary endpoint of all-cause mortality alone. DANISH trial — The Danish Study to Assess the Efficacy of ICDs in Patients with Non- Ischemic Systolic Heart Failure on Mortality (DANISH) randomly assigned 1116 patients with symptomatic systolic HF (LVEF <35 percent) not caused by ischemic heart disease to an ICD with guideline-directed optimal medical therapy or medical therapy alone [37]. Over a median follow-up of 5.6 years, no significant difference was noted in the primary outcome of total mortality (120 deaths [21.6 percent] in the ICD group compared with 131 deaths [23.4 percent] in the group without an ICD; HR 0.87, 95% CI 0.68-1.12). A significant reduction was noted in the prespecified secondary outcome of SCD in the group receiving ICDs (24 deaths [4.3 percent] compared with 46 sudden deaths [8.2 percent] in the no ICD group; HR 0.50, 95% CI 0.31-0.82), as well as nonsignificant trends toward reduction in total cardiovascular mortality and increased device infections in the ICD group. Compared with prior primary prevention ICD trials, the overall mortality rate of patients in the DANISH trial was low, likely due to improved medical therapy for HF (notably a much higher utilization of ACE-I/ARB and beta blockers than in the older trials) and the use of CRT, which was not available during the older primary prevention trials. Because of this, the DANISH trial may have been underpowered to show a mortality benefit of ICD therapy. Finally, as there are competing causes of death with increasing age, one might not expect the same benefit of ICD therapy in older patients, who may have greater comorbidities which could contribute to nonarrhythmic causes of death. Our experts feel that it would be premature to use data from the DANISH study as the sole basis to withhold potentially life-saving ICD therapy from all patients with nonischemic cardiomyopathy. Instead, the results actually support the use of ICDs in younger patients who have a cardiomyopathy not caused by ischemic heart disease. For those patients who are likely to have a strong response to CRT or who are not considered goodPaXoret-1-Co 1k ZU 11 aod LU) an ICD for primary prevention from the same original five ICD trials (CAT, AMIOVIRT, DEFINITE, SCD-HeFT, and COMPANION) as well as patients from the DANISH trial [38-46]. When considering all six trials collectively, each of the meta-analyses demonstrated a significant benefit of the ICD on all-cause mortality in patients with nonischemic cardiomyopathy (19 to 24 percent hazard reduction compared with medical therapy alone). When only patients who also received CRT in the COMPANION and DANISH trials were analyzed, there was a nonsignificant trend toward reduction in all-cause mortality among patients with an ICD (approximately 25 to 30 percent hazard reduction with nonsignificant confidence intervals) [38,40,43]. Despite the lack of a significant incremental benefit of the ICD in the two trials that included CRT, it is currently premature to withhold ICD therapy in all patients with nonischemic cardiomyopathy who require concomitant CRT. Adequately powered randomized studies are needed before recommending a change in current practice guidelines. GUIDELINE-DIRECTED MEDICAL THERAPY For patients who meet criteria for insertion of an implantable cardioverter-defibrillator (ICD) for the primary prevention of SCD, in the absence of a contraindication, we recommend optimizing guideline-directed medical therapy prior to ICD implantation. Heart failure therapy — Several of the components of appropriate medical therapy after a myocardial infarction (MI) reduce SCD as well as overall mortality. While these data are derived from trials in patients with ischemic heart disease, we can infer that many of the same benefits should apply to SCD risk reduction in patients with nonischemic cardiomyopathy. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST elevation acute coronary syndromes" and "Overview of the management of heart failure with reduced ejection fraction in adults’.) * Beta blockers - In addition to reducing overall mortality in patients with an acute MI, beta blockers also reduced the risk of SCD [47,48]. The SCD benefit is better established in patients with chronic HF. (See "Acute myocardial infarction: Role of beta blocker therap\ and "Ventricular arrhythmias: Overview in patients with heart failure and cardiomyopathy’, section on ‘Heart failure therapy’.) Post-MI patients with an ICD also appear to derive a benefit from beta blockers. In a cohort of 691 patients with ischemic cardiomyopathy who received an ICD in the MADIT-II trial, the 433 patients treated with a beta blocker had significantly lower mortality (hazard ratio [HR] 0.43) compared with those not taking beta blockers; additionally, patients in the highestPaNoret-1-1o ka ZU 181 aod LU) 0.80, 95% CI 0.70-0.92, absolute benefit approximately 1.4 percent) as well as overall and cardiovascular mortality [50]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Clinical trials".) + Angiotensin II receptor blockers - Angiotensin II receptor blockers (ARBs) are often used for patients who cannot tolerate ACE inhibitors. At appropriate doses, itis likely that ARBs reduce the risk of SCD to the same degree as ACE inhibitors [51]. (See "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use".) + Angiotensin receptor-neprilysin inhibitor - The combination of an ARB and neprilysin inhibitor, known as angiotensin receptor-neprilysin inhibitor or ARNI, is another therapy for use in patients with HF and reduced LVEF (HFrEF), A randomized double-blind trial (PARADIGM-HF) in patients with HFrEF found that sacubitril-valsartan reduced cardiovascular mortality and hospitalization for HF as well as all-cause mortality compared with a standard dose of the ACE inhibitor enalapril [52]. The ARNI combination is administered in conjunction with other HF therapies, in place of an ACE inhibitor or ARB. (See “Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults", Section on ‘Angiotensin receptor-neprilysin inhibitor’) * Statins - Statins given to patients who have had an acute MI improve overall mortality. Although data are limited and inconclusive, part of the benefit may result from a lower rate of SCD, which may reflect a direct effect of statin therapy [53-55]. (See "Low density lipoprotein-cholesterol (LDL-C) lowering after an acute coronary syndrome") + Mineralocorticoid receptor antagonists - Among post-MI patients who have left ventricular (LV) dysfunction and HF and/or diabetes, eplerenone significantly reduced both overall mortality and SCD (relative risk for SCD 0.79, 95% CI 0.64-0.97) [56]. (See "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults”, section on ‘Mineralocorticoid receptor antagonist.) Despite the proven benefits, some patients are not receiving guideline-directed medical therapy at the time of ICD implantation, In a 2011 study analyzing 175,757 first-time ICD recipients, using data from the National Cardiovascular Data Registry, 25.7 percent of ICD recipients without a documented contraindication were reported as not receiving optimal medical therapy at the time of ICD implantation, including 18.7 percent who were reported as not receiving an ACE inhibitor or ARB and 10.7 percent who were reported as not receiving a beta blocker [57]. While some of these gaps may reflect issues of coding and documentation, these data suggest an opportunity for significant improvement in the treatment of patients with evidence-based,PaNoro 1-10 1k ZU 11 aod LU) prophylactic ICD implantation remains uncertain. However, data demonstrate that a relevant proportion of patients with newly diagnosed HF may show recovery of LVEF >35 percent beyond three months after initiation of HF therapy, allowing left ventricular reverse remodeling to occur during intensified treatment [58] Antiarrhythmic drugs — Randomized clinical trials do not support the routine use of prophylactic antiarrhythmic drug therapy, other than beta blockers, to prevent SCD in patients with HF [1,59-62]. The lack of overall benefit from prophylactic antiarrhythmic drug therapy is due to both incomplete suppression of ventricular arrhythmias and the risk of proarrhythmia [60,61,63-67]. Given the established superiority of an ICD in high-risk patients, class I and class Ill antiarrhythmic drugs no longer have an established role for the primary prevention of SCD. ‘Among the antiarrhythmic drugs, amiodarone has the advantage of a relatively low rate of proarrhythmia, less negative inotropic effect, and higher efficacy for suppression of tachyarrhythmias. While amiodarone is not approved for use in the primary prevention of arrhythmias, this was a common off-label use of the drug [22]. In addition, amiodarone is frequently used for the treatment of atrial fibrillation as it is considered relatively "safe," from a cardiac standpoint, with low risk for proarrhythmia in the setting of HF [68]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on ‘Antiarrhythmic drugs' and "Amiodarone: Clinical uses", section on ‘Amiodarone for ventricular arrhythmias'.) SPECIAL POPULATIONS Class IV heart failure — Class IV HF is a state that may be transitory and therefore associated with heterogeneous prognosis. Once class IV HF is refractory (stage D HF), life expectancy is generally less than one year unless cardiac transplantation is performed or a left ventricular assist device is implanted. (See "Secondary prevention of sudden cardiac death in heart failur and cardiomyopathy", section on ‘Cardiac transplantation’) The role of implantable cardioverter-defibrillator (ICD) therapy for primary prevention of SCD in patients with New York Heart Association (NYHA) class IV HF with a narrow QRS complex has not been studied. NYHA class IV patients were generally excluded from randomized primary prevention ICD trials due to high expected mortality rate from pump failure, and only a small number were included in cardiac resynchronization therapy combined with ICD (CRT-D) trials. However, a nonrandomized series of patients awaiting cardiac transplantation suggested a higher likelihood of survival to transplantation with ICD therapy, regardless of whether the ICD indication was well established (69).PaNoret-1-1o ka ZU 181 aod LU) [2,69]. According to the 2017 Guideline for the Management of Patients with Ventricular Arrhythmias, "in patients with HFrEF who are awaiting heart transplant and who otherwise would not qualify for an ICD (eg, NYHA class IV and/or use of inotropes) with a plan to discharge home, an ICD is reasonable (class Ila recommendation, B-NR).” A wearable defibrillator vest may be considered as an alternative in selected patients [70,71]. Older adults and patients with comorbidities — Because of the competing risks of arrhythmic and nonarrhythmic death, some investigators have expressed concern that older adults and those with multiple or severe comorbidities might be less likely to derive benefit from an ICD [72-75]. The mean age of patients in randomized primary prevention ICD trials ranged from 60 to 67 years, and patients over 75 to 80 years comprised a relatively small proportion of these cohorts. Because most older adult patients as well as those patients with severe comorbidities (such as advanced kidney disease) were excluded from most of the major ICD trials, the survival benefit from ICD implantation in such populations is less welll defined. The decision to recommend an ICD should be made on a case-by-case basis based on shared decision making, taking into account patient values and preferences. Age or comorbidity alone should not be a sole exclusion for ICD implantation. As part of the 2017 AHA/ACC/HRS guideline for management of ventricular arrhythmias and prevention of SCD, a systematic review was performed to specifically assess the impact of primary prevention ICD therapy among older patients and patients with significant morbidities [26]. The following findings were noted: + Older adults - While the systematic review identified 10 studies of primary prevention ICD use among older adults, because of concerns about overlapping patients between some of the studies, the final "minimal overlap" meta-analysis included four studies with unique patient populations. Compared with patients without ICD implantation, patients who received a primary prevention ICD had a 25 percent reduction in total mortality (hazard ratio [HR] 0.75, 95% CI 0.67-0.83). + Patients with comorbidities - Among 10 studies of primary prevention ICD use in patients with a variety of comorbidities (including renal disease, chronic obstructive pulmonary disease, and diabetes, among others), ICD implantation for primary prevention was associated with a 28 percent reduction in total mortality (HR 0.72, 95% CI 0.65-0.79), with similar findings in the "minimal overlap" meta-analysis, which included only five studies (HR 0.71, 95% CI 0.61-0.82). + Patients with renal disease - Patients with chronic kidney disease requiring dialysis have increased mortality and reported high rates of SCD. Among five studies (two post-hocPaNoro 1-10 1k ZU 11 aod LU) been published evaluating the role of primary prevention ICDs in older patients and those with severe kidney disease. While randomized trial data are absent, clinicians have shown a preference for using the totally subcutaneous ICD (S-ICD) in patients with severe kidney disease (in particular among patients who undergo regular hemodialysis) in order to reduce the risk of intravascular infection in this population [77]. + Ina retrospective multi-center cohort of 300 patients receiving a primary prevention ICD or CRT-D, which included 150 patients 280 years old (mean age 82 years, 76 percent with one or fewer comorbidities) and 150 patients <80 years old (mean age 62 years, matched for gender and type of heart disease), similar numbers of patients received an appropriate shock (19.4 percent of older patients versus 21.6 percent of younger patients) with no significant difference in complication rates over mean follow-up of three years [78]. These data suggest that, compared with younger patients, primary prevention ICDs can be safely implanted in selected patients 280 years old with few or no comorbidities. * In patients on dialysis who did not meet standard indications for ICD therapy, the ICD2 trial was published suggesting no benefit from primary prevention ICDs [79]. In the ICD2 trial, 200 patients on dialysis who had an LVEF 235 percent without HF symptoms and no documented VT were randomized to ICD implantation with optimal medical therapy or to not receive an ICD. Following randomization of 188 patients, the trial was stopped prematurely due to futility, with no significant improvement among ICD recipients in five- year rates of SCD (9.7 versus 7.9 percent without ICD; HR 1.3; 95% CI 0.5-3.3) or overall survival (50.6 versus 54.4 percent without ICD; HR 1.0; 95% CI 0.7-1.5). While the results may be partially explained by the lower than expected observed rates of SCD in the study (annual rate of 2 percent versus expected rate of 5 to 6 percent), the data do not support extending primary prevention ICD use in dialysis beyond the standard indications. However, it should be noted that transvenous ICDs (often dual chamber systems) were utilized and significant complications occurred, including adverse events related to the ICD implantation procedure in 13 percent and ICD explantation (primarily due to bacteremia) in 7.5 percent. These results cannot necessarily be extrapolated to totally subcutaneous systems, which are frequently utilized in patients on dialysis as they appear to be associated with lower rates of bacteremia than transvenous systems. (See 'Our approach for patients with ischemic cardiomyopathy’ above and ‘Our approach for patients with nonischemic dilated cardiomyopathy’ above and "Subcutaneous implantable cardioverter defibrillators". GAPS IN THE GUIDELINESPaXoret-1-Co 1k ZU 11 aod LU) included in randomized clinical trials and may not be included in guideline documents [80]. This document includes discussion related to the following topics + Use of an ICD in patients with an abnormal troponin that is not due to a myocardial infarction (MI) + Use of an ICD within 40 days after a MI, such as patients with preexisting left ventricular (LY) dysfunction or those requiring non-elective permanent pacing * Use of an ICD within the first 90 days after revascularization, such as patients with preexisting LV dysfunction or those requiring non-elective permanent pacing + Use of an ICD within the first nine months after initial diagnosis of nonischemic cardiomyopathy Recommendations were made based on available evidence as well as consensus opinion. Many clinical scenarios where gaps in evidence exist for ICD therapy are also discussed in the 2013, Appropriate Use Criteria for Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy (CRT) [81]. Patients undergoing generator replacement with improved LVEF and/or no prior ICD therapies — An additional clinical scenario that is not fully covered in professional society guidelines and consensus documents is the management of patients who have received a primary prevention ICD who have improved or normalized LV function, have never received appropriate ICD therapy, and have either reached the point of elective replacement for their device or require reimplantation after system extraction (ie, due to infection) (72,82-87]. + Among a subset of 1273 patients from the SCD-HeFT trial (624 randomized to ICD, 649 randomized to placebo) who had repeat assessment of left ventricular ejection fraction (LVEF) at a mean of 13.5 months post-randomization, 371 patients (29 percent) showed improvement to LVEF >35 percent (186 [29.8 percent] in ICD group versus 185 [28.5 percent] in placebo group) [82]. There was a similar reduction in all-cause mortality with the ICD in both the LVEF <35 percent group (adjusted hazard ratio [HR] 0.64, 95% CI 0.48-0.85) and the LVEF >35 percent group (adjusted HR 0.62, 95% CI 0.29-1.30). * Among 752 patients from the MADIT-CRT study with mild HF symptoms, 7.3 percent had normalized LVEF to >50 percent after cardiac resynchronization therapy (CRT; so-called “super-responders"); these "super-responders" had a low rate of ventricular arrhythmias, with only 3 of 55 super-responders (5 percent) having treated VT (none requiring an ICD shock) at a mean follow-up of 2.2 years [83]. + Among 231 patients with an ICD placed for primary prevention, 26 percent had shown enough improvement in LVEF to no longer meet implant criteria at the time of electivePaNoret-1-1o ka ZU 181 aod LU) primary prevention ICD and had subsequent reassessment of LVEF, 40 percent of patients had >5 percent improvement in LVEF (over 4.9 years of follow-up), of whom 25 percent had improvement in LVEF to >35 percent [85]. Risk of an appropriate shock was significantly lower (but not completely eliminated) in patients with improved LVEF. + Among a cohort of 1421 patients with an ICD (49 percent primary prevention, 51 percent secondary prevention) scheduled to undergo generator replacement an average of 3.5, years following initial implantation, 471 patients (33 percent) had received an appropriate shock prior to replacement [88]. Following generator replacement, 435 patients (31 percent) received an appropriate ICD therapy during mean follow-up of 2.7 years. Patients with prior appropriate ICD therapy were significantly more likely to receive additional therapy following generator replacement (HR 3.0; 95% CI 2.4-3.7). With limited observational data and no randomized trial data to guide decision making for patients with normalized LVEF, clinicians need to weigh a number of factors when planning generator replacement or system reimplantation in such patients, including original indication, possibility of relapse in LV dysfunction, overall prognosis, comorbidities, and patient preference. The 2013 ACC/HRS/AHA Appropriate Use Criteria suggest that replacement of CRT-D with CRT-P devices "may be appropriate" in selected patients who underwent initial ICD implantation for primary prevention indications if substantial improvement in LV function is noted (LVEF now >35, percent, and particularly if 250 percent), if no clinically relevant ventricular arrhythmias have occurred [81]. However, due to the paucity of prospective data on this topic, it is also considered appropriate to replace a CRT-D device with a new CRT-D device in situations where LV function has improved [81]. PROGNOSTIC SIGNIFICANCE OF ICD SHOCKS AND DEVICE PROGRAMMING Among patients with HF receiving implantable cardioverter-defibrillators (ICDs) for primary prevention in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), an appropriate shock, as compared with no appropriate shock, was associated with substantially increased all-cause mortality (hazard ratio [HR] 5.7, 95% CI 4.0-8.1) [89]. An inappropriate shock, as compared with no inappropriate shock, was also associated with a significant increase in mortality (HR 2.0, 95% C1 1,3-3.1), The most common cause of death among patients who received any ICD shock was progressive HF. Other studies have also shown that appropriate or inappropriate shocks are associated with increased mortality [90,91]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy" and "Prognosis of heart failure’.)PaNoret-1-1o ka ZU 181 aod LU) long detection times, both of which were associated with fewer ICD shocks compared with conventional programming [92]. The Avoiding Defibrillator Therapies For Non-sustained Arrhythmias In ICD Patients (ADVANCE) III trial found a similar benefit for extended detection time in reducing both appropriate and inappropriate ICD shocks [93]. The 2015 HRS/EHRA/APHRS/SOLAECE Expert Consensus Statement on Optimal Implantable Cardioverter- Defibrillator Programming and Testing outlines the importance of proper ICD programming in reducing unnecessary therapy [24]. (See "Implantable cardioverter-defibrillators: Optimal programming".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Ventricular arrhythmias" and "Society guideline links: Cardiac implantable electronic devices".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5‘ to 6" grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10"" to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) * Basics topic (see “Patient education: Implantable cardioverter-defibrillators (The Basics)") * Beyond the Basics topic (see "Patient education: Implantable cardioverter-defibrillators (Beyond the Basics)") SUMMARY AND RECOMMENDATIONSPaNoro 1-10 1k ZU 11 aod LU) cardiomyopathy develop sustained ventricular tachyarrhythmias or SCD. Therefore, risk stratification of patients prior to considering ICD therapy is important for targeting therapy to patients at highest risk of SCD and minimizing the number of ICD implantations in patients who are unlikely to benefit. (See ‘Risk stratification strategies’ above.) ‘* Recommendations for selecting the optimal patients for ICD therapy are based largely upon the entry criteria in the major trials, Prior to recommending ICD therapy for the primary prevention of SCD, there should be a reasonable expectation of survival with a good functional status for at least one year regardless of the indication for ICD therapy. + For patients who meet criteria for insertion of an ICD for the primary prevention of SCD, in the absence of a contraindication, we recommend optimizing guideline- directed medical therapy with a beta blocker and either an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker prior to ICD implantation (Grade 4A), (See ‘Guideline-directed medical therapy’ above and "Overview of the management of heart failure with reduced ejection fraction in adults", + For patients with cardiomyopathy due to ischemic heart disease, left ventricular ejection fraction (LVEF) <35 percent, and associated heart failure (HF) with New York Heart Association (NYHA) functional class II or III status, we recommend ICD therapy for primary prevention of SCD (Grade 1A). Patients should be evaluated at least 40 days post-myocardial infarction (MI) and more than three months following revascularization. (See ‘Ischemic cardiomyopathy’ above.) + For patients with cardiomyopathy due to ischemic heart disease, LVEF <30 percent, and NYHA functional class I status, we recommend ICD therapy for primary prevention of SCD (Grade 1B). Patients should be evaluated at least 40 days post-MI and more than three months following revascularization. (See ‘Ischemic cardiomyopathy’ above.) + For patients with nonischemic dilated cardiomyopathy, LVEF £35 percent, and associated HF with NYHA functional class II or III status, we suggest ICD therapy for primary prevention of SCD rather than optimal medical therapy alone (Grade 2B). ICDs are very effective at reducing total mortality and mortality from SCD, although the benefits of an ICD on total mortality may be diminished in the setting of guideline- directed optimal medical therapy and cardiac resynchronization therapy (CRT). All patients receiving an ICD for primary prevention of SCD should be treated with at least three months of guideline-directed medical therapy prior to ICD implantation. (See ‘Nonischemic dilated cardiomyopathy’ above.)